OBJECTIVE: To explore the genetic variants and phenotypic characteristics of patients with Neurofibromatosis type I (NF1). METHODS: Twenty two NF1 patients who presented at Enze Medical (Center) Group in Taizhou between 2018 and 2024 were selected as the study subjects. Clinical phenotype and family history were collected for the patients. Whole exome sequencing (WES) was carried out for the 22 probands to screen the variants of NF1 gene. Candidate variants were verified by Sanger sequencing of their family members. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: K20230902). RESULTS: The 22 probands were diagnosed between the age of 5 months to 47 years old, and have all shown cafe au lait spots on their skin. Seventeen patients exhibited the phenotype at birth, and 11 had various degrees of neurofibromatosis. Among them, probands 1 and 13 underwent surgical resection of the tumor but had recurred, while proband 12 had amputation due to the huge size and serious impact of the neurofibroma and had no recurrence. Five patients had various degrees of scoliosis. In total 22 germline mutations and one somatic mutation were identified among the 22 families, with 5 variants unreported previously, including 1 nonsense mutation c.1603C>T (Q535*), 3 frameshift mutations [c.7268_7269delCA (Thr2423fs), c.2293del (Arg765Alafs*26), and c.5433_5438delinsGC (Phe1812ArgfsTer50)], and 1 deletion involving exons 41-44 of the NF1 gene and adjacent introns. Proband 13 was found to harbor germline mutation c.6796C>T (Gln2266Ter) and somatic mutation c.1019_1020del (Ser340Cysfs Ter12) in the peripheral blood and tumor tissue, respectively. Among the 22 NF1 probands, 6 had received treatment due to severe illness. Proband 1 had tumor resection in the right upper limb, but was found to have malignant lung tumor and died during follow-up. Proband 12 had multiple recurrence of neurofibroma in the left ring finger. Proband 4 underwent spinal correction surgery due to severe scoliosis. Proband 11 had died due to a central nervous system disease. Among the 22 germline mutations, 6 had led to the occurrence of truncated proteins, which may have a more severe impact on the phenotype. CONCLUSION This study investigated the genetic variants and clinical phenotypes of 22 NF1 families and identified 5 novel variants of the NF1 gene, which has expanded the genotypic and phenotypic spectra of the NF1. Preliminary studies have identified an association between truncated mutations, young age, and severe phenotypes, which may provide important clues for prognosis evaluation. For the clinical diagnosis and treatment of NF1, it is necessary to consider the phenotypic characteristics and genetic testing in combination with genetic counseling and long-term follow-up.
Humans ; Neurofibromatosis 1/pathology* ; Male ; Female ; Pedigree ; Adult ; Child ; Child, Preschool ; Middle Aged ; Adolescent ; Infant ; Young Adult ; Neurofibromin 1/genetics* ; Phenotype ; Asian People/genetics* ; Mutation ; Exome Sequencing ; East Asian People

Since its establishment in 2016, the National Rare Diseases Registry System of China (NRDRS) has accumulated valuable case data and bio-specimen for basic and clinical research on rare diseases in China. However, the emerging challenges in clinical diagnosis and treatment of rare diseases make it unable for data and resource platform to fully meet the diversified needs. Under this backdrop, we have developed a protocol to optimize and upgrade the system based on the core functions of the NRDRS platform. The goal is to leverage intelligent digital technologies to transform NRDRS into a new platform integrating multimodal data and auxiliary diagnostic and treatment functions. It is specified as the development and construction of "one platform and four intelligent tools." Currently, we have upgraded and developed NRDRS platform, intelligent tool for genotype-phenotype analysis of rare diseases, AI-assisted diagnostic tool for rare diseases, remote multidisciplinary diagnosis and teaching tool for rare diseases, drug screening and validation tool for rare diseases. The next step will focus on the promotion of the application of these tools in clinical settings in order to address the issue of severe imbalance in the allocation of resources for the diagnosis and treatment of rare diseases. This article provides an overview of the digital and intelligent upgrades of the NRDRS, the trials in applications in clinical settings, and direction in the future.

The Shanghai-style pediatric Tuina(Chinese therapeutic massage)school,a renowned academic school of pediatric Tuina in China,was founded by Professor JIN Yicheng,a mentor of the National Senior Traditional Chinese Medicine(TCM)Experts'Clinical Experience Inheritance Class and a distinguished TCM practitioner in Shanghai.This academic school has now been perpetuated through four generations.Prof.JIN Yicheng,a pioneering leader in modern China's pediatric Tuina,has dedicated sixty years to medical practice with unwavering benevolence and adherence to"principled innovation".While delving into traditional and ancient teachings,he has also embraced contemporary advancements.Building upon the essence of traditional pediatric Tuina,he integrated distinctive techniques from various Tuina schools,including the Yi Zhi Chan Tuina school,rolling manipulation Tuina school,and Neigong Tuina school.He also assimilated the quintessence of historical pediatric Tuina literature,the experience of modern Shanghai-based pediatric Tuina masters,and folk techniques while incorporating his years of clinical insights.This synthesis finally led to the formulation of the academic thought of"reinforcing healthy Qi and unblocking regulation"in Shanghai-style pediatric Tuina that guides clinical practice.Specifically,he comprehensively applies techniques such as"unblocking regulation of Zang-Fu organs","unblocking regulation of the four seas","unblocking regulation of the water and fire",and"unblocking regulation of the back"to the prevention and treatment of pediatric diseases across internal medicine,external medicine,orthopedics,and otolaryngology,which has significantly enhanced clinical efficacy and expanded the applicable age range and scope of Tuina for pediatric health issues,more aligning with the characteristics of children and adolescents'health challenges and current clinical demands,and paving a new way in preserving and developing traditional pediatric Tuina.

Objective To explore the construction of a scientific and reasonable performance appraisal and evaluation system for clinical department heads in public hospitals,so as to provide reference for improving the operational efficiency and medical service quality of hospitals.Methods Preliminary construction of the indicator system through the literature research method,using the Delphi method to conduct two rounds of correspondence with 13 experts in related fields,screening and revising the performance appraisal evaluation indicators,and establishing the final indicator system.Results Formation of a performance appraisal and evaluation system for heads of clinical departments that includes 7 one-vote veto indicators,4 first-level indicators,19 medical and 24 surgical second-level indicators and 3 plus indicators,with the authority coefficients of the two rounds of expert consultation at 0.89 and 0.90,and the harmonization coefficients at 0.504 and 0.630,respectively,and with good results in consistency tests for indicators at all levels.Conclusion The performance appraisal and evaluation system for clinical department chiefs has good science and feasibility.It has played a positive role in promoting the connotative construction of the hospital and improving the management efficiency of the hospital,and can provide a reference for hospital management practice.

OBJECTIVE: To determine the types of genetic variants in six Chinese pedigrees affected with Marfan syndrome (MFS) and analyze their clinical characteristics and molecular pathogenesis. METHODS: Six MFS pedigrees presented at the Taizhou Enze Medical Center (Group) between 2017 and 2022 were selected as the study subjects. Clinical data of pedigrees were retrospectively analyzed. Peripheral blood samples were collected from the probands and their family members for the extraction of genomic DNA. Whole exome sequencing (WES) was carried out. Candidate variants of the FBN1 gene were verified by Sanger sequencing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), pathogenicity of the candidate variants was assessed. AlphaFold3 and PyMOL software were used for homology modeling of the FBN1 protein and analysis of its three-dimensional structure and amino acid sequence conservation. This study was approved by the Medical Ethics Committee of Taizhou Enze Medical Center (Group) (Ethics No. 20231002). RESULTS: Cardiovascular system abnormalities were noted in all pedigrees, ocular abnormalities were present in pedigrees 2 and 5, skeletal system abnormalities were presented in pedigrees 1, and 4 to 6. FBN1 gene mutations were identified in all pedigrees, including c.1957_1958dupGT (p.Asp654fs), c.5014T>A (p.Cys1672Ser), c.8135delC (p.Pro2712fs), c.2302G>T (p.Glu768*), c.3473A>G (p.Glu1158Gly) and c.6169C>T (p.Arg2057*), with each involving a different exon. Four variants were rated as pathogenic, one as likely pathogenic, and one as variant of uncertain significance. Among these, c.5014T>A (p.Cys1672Ser), c.1957_1958dupGT (p.Asp654fs), c.8135delC (p.Pro2712fs), and c.2302G>T (p.Glu768*) were unreported previously. Bioinformatic analysis with SIFT and PolyPhen-2 predicted that the c.5014T>A (p.Cys1672Ser) and c.3473A>G (p.Glu1158Gly) variants were deleterious. Protein homologous sequence alignment analysis revealed that the four novel mutation sites are highly conserved across various species. Homology modeling of the FBN1 protein three-dimensional structure indicated that the six variant sites in the amino acid sequence are all close to hydrogen bonds and may alter the secondary and tertiary structures to varying degrees, thereby confirmed the relationship between the variants and MFS. CONCLUSION Four novel variants of the FBN1 gene have been discovered in this study, which has enriched the mutational and phenotypic spectrum of MFS and provided a basis for disease diagnosis and genetic counseling.
Adolescent ; Adult ; Child ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; China ; East Asian People/genetics* ; Exome Sequencing ; Fibrillin-1/genetics* ; Marfan Syndrome/genetics* ; Mutation ; Pedigree ; Retrospective Studies ; Adipokines

Objective:To evaluate the effect of robot-assisted laparoscopic technology via abdominal approach for patients with primary retroperitoneal tumors.Methods:A retrospective cohort analysis was conducted for the clinical data of 71 patients who underwent robot-assisted laparoscopic resection of primary retroperitoneal tumor via abdominal approach at the Department of Urology of Sir Run Run Shaw Hospital,Zhejiang University School of Medicine from January 2015 to December 2023. There were 35 male and 36 female patients. The age ( M(IQR)) was 56(21) years (range: 21 to 83 years). The median tumor diameter was 46 (31) mm (range: 15 to 134 mm). Postoperative pathology revealed 58 benign and 13 malignant cases. Patients were divided into non-adherent group ( n=47) and adherent group ( n=24) based on whether the tumor was adhered to major organs or vessels. Perioperative and postoperative situation were compared between the two groups. Data comparisons were conducted using independent samples t-test for normally distributed continuous variables, Mann-Whitney U tests for non-normally distributed data, χ2 test or Fisher′s exact test for categorical variables. Kaplan-Meier survival analysis was employed to estimate 3-year recurrence or metastasis rate and 3-year mortality rate. Results:Operative time was 120(60) minutes (range: 45 to 440 minutes), intraoperative blood loss was 50 (80) ml (range: 10 to 2 000 ml). The median change of intraoperative mean arterial pressure was 40 (19) mmHg(1 mmHg=0.133 kPa)(range: 10 to 112 mmHg). Intraoperative blood transfusion was required in 7 cases, whereas 64 cases did not necessitate transfusion. The change in hemoglobin levels before and after surgery was (17.9±13.6) g/L (range:-16 to 53 g/L), and the median change in serum creatinine levels was 2.0 (14.5) μmol/L (range:-71.0 to 100.4 μmol/L). Postoperative fasting duration was 2.0 (1.5) days (range: 1 to 6 days), and the median hospital stay was 10.0 (7.5) days (range: 4 to 24 days). No perioperative mortality occurred in any of the patients. The non-adherent group had shorter operation time, less estimated blood loss, lower blood transfusion rate, smaller delta value of hemoglobin before and after surgery, larger delta value of creatinine before and after surgery, fewer postoperative complications, shorter postoperative fasting time, and shorter length of hospital stay than the adherent group(all P<0.05), while there was no significant difference in mean arterial pressure fluctuation between the two groups ( P>0.05). Follow-up data were available for 69 patients, with a median follow-up duration of 39 (43) months (range: 4 to 88 months). Among these patients, 40 completed the 3-year follow-up. The 3-year recurrence or metastasis rate was 10.14%, and the 3-year mortality rate was 2.90%. Conclusions:Robot-assisted laparoscopic technology via abdominal approach for resection of primary retroperitoneal tumors is safe and feasible. It can also achieve secure surgical outcome for primary retroperitoneal tumors adherent to surrounding organs or vessels, albeit with increased surgical complexity and slower postoperative recovery compared to non-adherent cases.

Immune checkpoint inhibitors(ICIs)have revolutionized cancer therapy,but their use is frequently complicated by immune-related adverse events(irAEs),which often require management with corticosteroids or additional immunosuppressive agents.The prognostic impact of these therapeutic strategies in the setting of irAEs has not been systematically elucidated.This systematic review and meta-analysis aimed to evaluate the impact of corticosteroid(CS)and second-line immunosuppressant(IM)use on survival outcomes among patients who developed irAEs during ICI therapy.Following a preregistered protocol(PROSPERO CRD1144835),we systematically searched PubMed,Embase,Web of Science,Cochrane Library,SinoMed,CNKI and Wanfang to identify studies published in the past 10 years(up to May 2025)reporting on the association between CS and IM use and survival outcomes in ICI-treated patients with irAEs.Two reviewers independently performed study selection,data extraction,and quality assessment.Meta-analyses were performed using R software.A total of 11 studies comprising 7 255 patients were included.Meta-analysis showed that CS use versus no use was not significantly associated with overall survival(OS)(HR=0.73,95%CI:0.45-1.18)or progression-free survival(PFS)(HR=0.68,95%CI:0.00-98.01).For post-irAE survival outcomes,higher cumulative CS dose(per 1 000 mg increment)was associated with a mild protective effect on post-irAE OS(HR=0.95,95%CI:0.92-0.98)and post-irAE PFS(HR=0.96,95%CI:0.94-0.99).In contrast to CS alone,IM use in combination with CS was associated with significantly increased risk of disease progression or death for post-irAE OS(HR=1.40,95%CI:1.11-1.76)and post-irAE PFS(HR=1.32,95%CI:1.08-1.62).Sensitivity analyses demonstrated good robustness of the main significant results.Current evidence suggests that CS and IM management strategies may differentially affect survival outcomes in patients with irAEs following ICI therapy.Increased cumulative CS dose is not associated with worse outcomes,whereas the addition of second-line IMs may increase the risk of adverse survival outcomes.Further prospective studies are warranted to optimize irAE management strategies and to balance the risks of immunosuppressive therapy with anticancer efficacy.

Objective To explore the construction of a scientific and reasonable performance appraisal and evaluation system for clinical department heads in public hospitals,so as to provide reference for improving the operational efficiency and medical service quality of hospitals.Methods Preliminary construction of the indicator system through the literature research method,using the Delphi method to conduct two rounds of correspondence with 13 experts in related fields,screening and revising the performance appraisal evaluation indicators,and establishing the final indicator system.Results Formation of a performance appraisal and evaluation system for heads of clinical departments that includes 7 one-vote veto indicators,4 first-level indicators,19 medical and 24 surgical second-level indicators and 3 plus indicators,with the authority coefficients of the two rounds of expert consultation at 0.89 and 0.90,and the harmonization coefficients at 0.504 and 0.630,respectively,and with good results in consistency tests for indicators at all levels.Conclusion The performance appraisal and evaluation system for clinical department chiefs has good science and feasibility.It has played a positive role in promoting the connotative construction of the hospital and improving the management efficiency of the hospital,and can provide a reference for hospital management practice.

Along with the continuous promotion of the national medical reform policy,high-quality development has become an important goal for the sustainable development of hospitals.Day surgery,with its advantages of high efficiency in the use of medical resources and ease of post-operative follow-up and management,has gradually become an important tool for hospitals to achieve high-quality development.As a pioneer in the management of day surgery in China,the Sir Run Run Shaw Hospital has been implementing the theory of Total Quality Management,focusing on patients,and continuously innovating and exploring the management mode of day surgery,with a view to providing a reference for the improvement of the quality of medical services and management of day surgery in China.

Immune checkpoint inhibitors(ICIs)have revolutionized cancer therapy,but their use is frequently complicated by immune-related adverse events(irAEs),which often require management with corticosteroids or additional immunosuppressive agents.The prognostic impact of these therapeutic strategies in the setting of irAEs has not been systematically elucidated.This systematic review and meta-analysis aimed to evaluate the impact of corticosteroid(CS)and second-line immunosuppressant(IM)use on survival outcomes among patients who developed irAEs during ICI therapy.Following a preregistered protocol(PROSPERO CRD1144835),we systematically searched PubMed,Embase,Web of Science,Cochrane Library,SinoMed,CNKI and Wanfang to identify studies published in the past 10 years(up to May 2025)reporting on the association between CS and IM use and survival outcomes in ICI-treated patients with irAEs.Two reviewers independently performed study selection,data extraction,and quality assessment.Meta-analyses were performed using R software.A total of 11 studies comprising 7 255 patients were included.Meta-analysis showed that CS use versus no use was not significantly associated with overall survival(OS)(HR=0.73,95%CI:0.45-1.18)or progression-free survival(PFS)(HR=0.68,95%CI:0.00-98.01).For post-irAE survival outcomes,higher cumulative CS dose(per 1 000 mg increment)was associated with a mild protective effect on post-irAE OS(HR=0.95,95%CI:0.92-0.98)and post-irAE PFS(HR=0.96,95%CI:0.94-0.99).In contrast to CS alone,IM use in combination with CS was associated with significantly increased risk of disease progression or death for post-irAE OS(HR=1.40,95%CI:1.11-1.76)and post-irAE PFS(HR=1.32,95%CI:1.08-1.62).Sensitivity analyses demonstrated good robustness of the main significant results.Current evidence suggests that CS and IM management strategies may differentially affect survival outcomes in patients with irAEs following ICI therapy.Increased cumulative CS dose is not associated with worse outcomes,whereas the addition of second-line IMs may increase the risk of adverse survival outcomes.Further prospective studies are warranted to optimize irAE management strategies and to balance the risks of immunosuppressive therapy with anticancer efficacy.